The invention relates to non-yellowing and non-coloring biocidal compositions used in or on industrial and natural products to prevent attack by micro-organisms, in particular algae, fungi and bacteria; such industrial or natural products are e.g. paint and lacquer films, plasters, adhesives, glues, leather, textiles, natural fibers, etc. The invention relates more particularly to antimicrobial compositions of synergistic increased activity to protect colorless, white or pale-colored substrates and coating materials where yellowing, discoloring or color changes are not acceptable.
It is known e.g. from the U.S. Pat. Nos. 3,615,745 (Oct. 26, 1971), 3,663,623 (May 16, 1972), 3,792,091 (Feb. 12, 1974) and 3,806,351 (Apr. 23, 1974) that diiodomethyl sulfones of the formula (I) R(CH.sub.2).sub.n SO.sub.2 CHI.sub.2, wherein n is an integer from 0 to 4 and R is selected from the group alkyl, cycloalkyl, phenyl, naphthyl, loweralkylphenyl, polyloweralkylphenyl, loweralkoxyphenyl, monohalophenyl, polyhalophenyl, haloloweralkylphenyl, halonitrophenyl, nitrophenyl, nitroloweralkylphenyl, anilino, anilinophenyl, and anilamidophenyl, exhibit good antimicrobial activity. Said diiodomethyl sulfones have been proposed for the production or coating of materials as mentioned above. The entire disclosures of the four above mentioned United States patents are hereby incorporated by reference and relied upon.
However, in practical use the compositions have the serious draw-back that the diiodomethyl sulfones are yellowing and produce discoloring effects on the materials to be protected, though the diiodomethyl sulfones themselves can be colorless.
It was not possible to determine the chemical reaction causing the yellowing of the diiodomethyl sulfones. While said yellowing occurs even in the absence of any light or other environmental factors, the yellowing is enhanced by light, temperature and the influence of weather conditions. It is assumed that the yellowing and discoloring is caused by a degradation mechanism of the diiodomethyl sulfone which is initiated and/or accelerated by a variety of factors including light, heat and substances contained in the natural or industrial host materials to be protected against the attack of micro-organisms.
Due to the serious draw-back of yellowing, antimicrobial compositions comprising diiodomethyl sulfones were not applicable to protect colorless, white or pale-colored host materials and coatings against the attack of micro-organisms. The application of antimicrobial compositions comprising diiodomethyl sulfones were restricted to the rare cases where the yellowing or discoloring was acceptable, e.g. to protect viable seed potential hosts or in paints having a rather dark inherent color.
There is another group of chemical compounds exhibiting good biocidal, in particular fungicidal properties, viz. derivatives of the dithiocarbamic acids having the general formula II: ##STR1## wherein R.sub.1 and R.sub.2 represent organic radicals, and the esters and salts of said dithiocarbamic acid, which compounds are generally referred to as "dithiocarbamates". Said dithiocarbamates have found a widespread use as agricultural fungicides. It is known that dithiocarbamates form strongly colored complexes with heavy metal ions. When using dithiocarbamates as fungicides, e.g. in white or pale-colored paints and coatings, there is always the risk of color formation because of substrates in coating materials containing traces of heavy metals as impurities.
It is an object of this invention to provide a non-yellowing and non-coloring composition comprising diiodomethyl sulfones to protect potential natural and industrial host materials against the attack of micro-organisms, in particular bacteria, algae and fungi.
It is another object of this invention to provide a non-coloring antimicrobial composition comprising diiodomethyl sulfones having enhanced antimicrobial activity.
It is a further object of this invention to provide a method of protecting potential natural or industrial host material against attack by micro-organisms, in particular bacteria, algae and fungi comprising treating said host material with diiodomethyl sulfones and preventing the yellowing and discoloring effect of the diiodomethyl sulfones. It is still another object of this invention to provide a composition which will protect painted surfaces, plasters and textiles against the attack by micro-organisms, in particular bacteria, algae and fungi.
These and other objects which will become apparent from the following description and examples are attained through the provision of an antimicrobial composition comprising a diiodomethylsulfone of the formula (I) R(CH.sub.2).sub.n SO.sub.2 CHI.sub.2, wherein n is an integer from 0 to 4 and R is selected from the group alkyl, cycloalkyl, phenyl, naphthyl, loweralkylphenyl, polyloweralkylphenyl, loweralkoxyphenyl, monohalophenyl, polyhalophenyl, haloloweralkylphenyl, halonitrophenyl, nitrophenyl, nitroloweralkylphenyl, anilino, anilinophenyl, and anilamidophenyl, and to prevent the yellowing and/or the discoloring of the diiodomethyl sulfone a compound containing a reactive sulfide or sulfhydryl group.
The term "loweralkyl38 is intended to include those substituents having from 1 to 7 carbon atoms, preferably from 1 to 4 carbon atoms.
Examples of compound within formula (I) are 4-chlorophenyl diiodomethyl sulfone, p-tolyldiiodomethyl sulfone, phenyl-diiodomethyl sulfone, 4-t-butylphenyl diiodomethyl sulfone, 3,4-dichlorophenyl diiodomethyl sulfone, 4-methoxybenzyl diiodomethyl sulfone, n-octyldiiodomethyl sulfone, 2-nitro-4-chlorophenyl-diiodomethyl sulfone, 2-nitro-4-methylphenyl-diiodomethyl sulfone, 4-bromophenyl diiodomethyl sulfone, 2-methyl-4-p-t-butylphenyl diiodomethyl sulfone, p-anisyl diiodomethyl sulfone, 2-naphthyl diiodomethyl sulfone, 1-naphthyl diiodomethyl sulfone, 2-methyl-4-chlorophenyl diiodomethyl sulfone, 3,4-dimethylphenyl diiodomethyl sulfone, ethyl diiodomethyl sulfone, 4-fluorophenyl diiodomethyl sulfone, 4-iodophenyl diiodomethyl sulfone, 3,4-dibromophenyl diiodomethyl sulfone, 3-chloro-4-bromophenyl diiodomethyl sulfone, 2,4,5-trichlorophenyl diiodomethyl sulfone, cyclopentyl diiodomethyl sulfone, p-methylcyclohexyl diiodomethyl sulfone, butyl diiodomethyl sulfone, amyl diiodomethyl sulfone, p-heptylphenyl diiodomethyl sulfone, 2,4-diethylphenyl diiodomethyl sulfone, 2-methyl-4-chlorophenyl diiodomethyl sulfone, 2-chloro-4-butylphenyl diiodomethyl sulfone, 3-nitrophenyl diiodomethyl sulfone, benzyl diiodomethyl sulfone, phenethyl diiodomethyl sulfone, phenylbutyl diiodomethyl sulfone, p-aminophenyl diiodomethyl sulfone, p-aminodiphenyl diiodomethyl sulfone, 2,4-difluorophenyl diiodomethyl sulfone, 4-ethoxyphenyl diiodomethyl sulfone, 4-butoxyphenyl diiodomethyl sulfone, anilamidophenyl diiodomethyl sulfone, 4-(methylamido)-phenyl diiodomethyl sulfone, n-heptyl diiodomethyl sulfone, 3-tolyl diiodomethyl sulfone, 2-tolyl diiodomethyl sulfone, 2-methyl-4-bromophenyl diiodomethyl sulfone, 3-methyl-4-bromophenyl diiodomethyl sulfone, 2,4-dimethylphenyl diiodomethyl sulfone, t-butyl diiodomethyl sulfone, 2-methyl-4-butylphenyl diiodomethyl sulfone, 4-chlorobenzyl diiodomethyl sulfone, 4-nitrophenyl diiodomethyl sulfone, 2-isopropylphenyl diiodomethyl sulfone, cyclohexyl diiodomethyl sulfone, 4-methylbenzyl diiodomethyl sulfone, n-hexyl diiodomethyl sulfone, n-propyl diiodomethyl sulfone, 4-bromobenzyl diiodomethyl sulfone, 4-methoxybenzyl diiodomethyl sulfone, 3-chlorobenzyl diioclomethyl sulfone, 3-bromobenzyl diiodomethyl sulfone, 2-naphthylmethyl diiodomethyl sulfone, 1-phenyl-3-(diiodomethylsulfonyl) propane, isobutyl diiodomethyl sulfone, 3,4-dimethylbenzyl diiodomethyl sulfone, 3,3-dimethylpropyl diiodomethyl sulfone, 2,2,4,4-tetramethylbutyl diiodomethyl sulfone.
According to a preferred embodiment of the invention, the antimicrobial composition comprises a compound containing a reactive sulfide or sulfhydryl group a compound having the general formula III, R.sup.9 --S--X, wherein X is selected from the group consisting of hydrogen, R.sup.9 --S-- and R.sup.9 --, and R.sup.9 is selected from the group consisting of hydrogen, an equivalent of a metal, e.g. sodium, potassium, zinc, manganese, calcium, zirconium, magnesium, iron, and an organic radical.
According to a particularly preferred embodiment of the invention the antimicrobial composition comprises a diiodomethyl sulfone of the formula R(CH.sub.2).sub.n SO.sub.2 CHI.sub.2, wherein n and R have the meaning set forth above and as a compound to prevent the yellowing and the discoloring of the diiodomethyl sulfone and to impart enhanced activity against microorganisms to the composition a dithiocarbamate having the following general formula IV: ##STR2## wherein R.sub.1 is selected from the group consisting of hydrogen and lower alkyl, e.g. methyl, ethyl, propyl, isopropyl, sec. butyl, butyl, t-butyl, amyl, hexyl, heptyl, R.sub.2 is selected from the group consisting of hydrogen, lower alkyl, as just set forth a residue of the general formula IV a: ##STR3## wherein Alk represents an alkylene group having 1 to 6, preferably 2 to 3, carbon atoms and a residue of the formula V: ##STR4## wherein R.sub.6 is selected from the group consisting of hydrogen, loweralkyl and hydroxyloweralkyl and R.sub.7 is selected from the group consisting of hydrogen, loweralkyl and hydroxyloweralkyl or wherein R.sub.1 and R.sub.2 together with the nitrogen atom to which they are attached form a heterocyclic ring having 4 to 6 carbon atoms, and R.sub.3 is selected from the group consisting of hydrogen, an equivalent of a metal atom such as those set forth above a group R.sub.8 --, R.sub.8 CH.sub.2 -- or R.sub.8 --S--, wherein R.sub.8 is an organic radical, preferably the group ##STR5## wherein R.sub.1 and R.sub.2 have the same meaning as above, wherein R.sub.3 and R.sub.7 together represent an optionally substituted methylene bridge.
Representative compounds containing at least one reactive sulfide or sulfhydryl group to be combined with the above diiodomethyl sulfones include zinc sulfide, lithopones, (a technical product containing zinc sulfide and barium sulfate), higheralkylmercaptides, thioglycolic acid and its esters thiopropionic acid and its esters thioureas, thiophenyls and dithiocarbamates.
Among the higher alkyl mercaptides and mercaptans are sodium octyl mercaptide, sodium decyl mercaptide, sodium dodecyl mercaptide, sodium octadecyl mercaptide, sodium eicosanyl mercaptide, potassium hexadecyl mercaptide, zinc octadecyl mercaptide, ferric mercaptide, octyl mercaptan, lauryl mercaptan, cetyl mercaptan, octadecyl mercaptan. Ester of thioglycolic acid and thiopropionic acid include methyl thioglycolate, ethyl thioglycolate, butyl thioglycolate, octyl thioglycolate, 2-ethylhexyl thiopropionate, octadecyl thioproponate, 2-ethyl hexyl thioglycolate, octadecyl thioglycolate. Thioureas include thiourea itself, methyl thiourea, ethyl thiourea, 1,3-diethyl thiourea, trimethyl thiourea, butyl thiourea. Thiophenols include thiophenol itself, p-methylthiophenol and thionaphthol.
Representative dithiocarbamates showing synergistic increase of activity in combination with diiodomethyl sulfones are listed in Table I.
Other dithiocarbamates include disodium-ethylene-bis-dithiocarbamate, ferric dimethyldithiocarbamate, zinc-N,N-diethyl dithiocarbamate, sodium-N,N-dibutyl dithiocarbamate, zinc-N,N'-hexamethylene-1,6-bis(dithiocarbamate), sodium-N,N'-tetramethylene-1,4-bis(dithiocarbamate), sodium-N-[N'-bis(hydroxymethyl)-aminomethyl]-N-methyl dithiocarbamate, zinc N-methyl, N-heptyl dithiocarbamate, tetraethyl thiuram disulfide, sodium N-methyl dithiocarbamate, sodium salt of 1-piperidinecarbodithioic acid, zinc salt of pyrrolidinecarbodithioic acid, 4-morpholinecarbodithioic acid-2-hydroxyethylester, disodiumpiperazine-bis-(dithiocarbamate), ethylenethiuram monosulfide, carbethoxydimethyldithiocarbamate, 2,4dinitrophenyl-N,N-dimethyldithiocarbamate, S-phenylacyl-N,N-dimethyldithiocarbamate, S-(4-nitrobenzoyl)-N,N-dimethyldithiocarbamate, S-(1-methyl-1-carboxyethyl)-pyrroline-N-carbodithioate, S-carbomethoxy-N,N-dimethyldithiocarbamate, S-ethyl-N,N-dimethyldithiocarbamate, S-acetonyl-N,N-dimethyldithiocarbamate, S-(2-isonitrosopropyl)-N,N-dimethyldithiocarbamate, S-cyanomethyl-N,N-dimethyldithiocarbamate, ethoxycarbonyl-2,4,4-trimethyltetramethylenedithiocarbamate, di-n-butoxycarbonyl-2,5-dimethylpiperatine-1,4-biscarbodithionate, isopropoxycarbonyltetramethylenedithiocarbamate, N-methyl-N-phenyldithiocarbamic acid acetic acid ester, diethyldithiocarbamic acid 2-hydroxyethyl ester, ethylenethiuramidisulfide.
Considering the materials in Table I each compound 1 to 10 may be combined with each compound A to L. It is obvious from the above that any other diiodomethyl sulfone comprised by the formula I can be combined with any other compound containing a reactive sulfide or sulfhydryl group.
TABLE I __________________________________________________________________________ (1) (4-chlorophenyl- (A) Na-N,N-dimethyl- diiodomethyl sulfone dithiocarbamate (2) 4-tolyl-diiodomethyl (B) zinc-N,N'-ethylene-bis- sulfone (dithiocarbamate) (3) phenyl-diiodomethyl (C) tetramethyl-triuramedisulfide sulfone (4) 4-tert.-butylphenyl- (D) zinc-N,N'-propylene-1,2-bis- diiodomethyl sulfone (dithiocarbamate) (5) 3,4-dichlorophenyl- (E) 3,5-dimethyl-1,3,5-2H-tetrahydro- diiodomethyl sulfone thiadiazine-2-thione (6) cyclohexyldiiodo- (F) S,S'-di-(methylxanthogenyl)- methyl sulfone ethylene-bis-(dithiocarbamate) (7) 4-methoxybenzyl- (G) zinc-N,N-dimethyldithio- diiodomethyl sulfone carbamate (8) n-octyl- (H) manganese-N,N'-ethylene-bis- diiodomethyl sulfone dithiocarbamate (9) 2-nitro-4-chloro- (I) S-benzyl-N,N-dimethyl- phenyldiiodomethyl dithiocarbamate sulfone (10) 2-nitro-4-methyl- (K) carbethoxytetramethylene- phenyldiiodomethyl dithiocarbamate sulfone (L) sodium-N-[N'-methyl-N'- hydroxymethyl-aminomethylene]- N-methyldithiocarbamate __________________________________________________________________________
Depending on the compounds used the proportion between diiodomethyl sulfones (a) and the compounds (b) containing a reactive sulfide or sulfhydryl group may vary; said proportion is preferably expressed in molar equivalent ratios (a:b). Although a small amount of the compound containing a reactive sulfide or sulfhydryl group is sufficient to considerably reduce the discoloring effect or diiodomethyl sulfones, the best effects are obtained within a molar equivalent ratio of 1 mol (a): 0.5-4 moles (b), particularly good results are usually found at molar equivalent ratios of 1 mole (a): 1.8 - 2.4 moles (b), or preferably by using a molar equivalent ratio of approximately 1:2.
The compounds (a) and (b) can either be premixed and then incorporated into a coating composition or (a) and (b) can be added separately at various stages of preparing the coating composition. In cases where the compounds are soluble in a solvent compatible with the coating compositions, the compounds can be dissolved in the solvent and the obtained solution can be added to the finished coating composition, e.g. a latex paint, simply by mixing the solution with the coating composition. In cases where no solvent compatible with the coating compositions can be found, it is preferable to prepare a paste of compounds (a) and (b) and incorporating said paste (e.g. simply by stirring) into the coating compositions.
The total quantity of compounds (a and b) employed and the concentration at which the mixture is applied to protect potential host materials varies with the application, the degree of protection required, and can also be dictated by economic considerations. Normally, quantities ranging from 0.05 to 2 percent by weight are used in coating compositions such as paints, plasters, adhesives, leather and textile finishings and sprays.